Defining the caprine ¿d T cell WC1 multigenic array and evaluation of its expressed sequences and gene structure conservation among goat breeds and relative to cattle

Authors: YIRSAW, ALEHEGNE - University Of Massachusetts, Amherst; GILLESPIE, ALEXANDRA - University Of Massachusetts, Amherst; ZHANG, FENGQUI - University Of Massachusetts, Amherst; Smith, Timothy - Tim; Bickhart, Derek; GUNASEKARAN, KARTHICK - University Of Massachusetts, Amherst; AMIR, MARIA - University Of Massachusetts, Amherst; PARK, HAEREE - University Of Massachusetts, Amherst; TELFER, JANICE - University Of Massachusetts, Amherst; BALDWIN, CYNTHIA - University Of Massachusetts, Amherst

Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2022
Publication Date: N/A
Citation: N/A

Interpretive Summary: The immune systems of ruminants have many similarities to those of humans and other mammals, but there can be important differences. One family of ruminant-specific immune-related genes known as the “Workshop Cluster 1” (WC1) family encode molecules that are part of a superfamily of scavenger receptors important for a class of immune cells called T cells in recognizing and binding to pathogens. The WC1 family is most thoroughly described in cattle, where members of the family have been shown to play roles in immediate immune response to infection. While the existence of WC1 molecules has been demonstrated in goats, the genetic loci encoding them have not previously been described. In this manuscript, the number and organization of WC1 genes are described, with supporting evidence of functionality, and the loci is compared to the cattle loci to reveal some similarities while identifying potentially important differences. The research may impact development of next generation vaccines designed to activate the immediate immune response, which may have advantages over traditional vaccine methods that target the memory cell population that are slower to respond to infection.

Technical Abstract: Background. Workshop Cluster 1 (WC1) molecules are part of the scavenger receptor cysteine rich (SRCR) superfamily and act as hybrid co-receptors for the gd T cell receptor and as pattern recognition receptors for binding pathogens. These members of the CD163 family are expressed on the majority of gd T cells in the blood of ruminants and appear to form an important part of immunity against infections. The cattle genome contains 13 members of the WC1 family. While the presence of WC1+ gd T cells in the blood of goats had been demonstrated using monoclonal antibodies there was no information available about the goat WC1 gene family. Results. The caprine gd T cell co-receptor WC1 multigenic array was characterized with regard to the number, structure and expression of genes, for sequence similarity compared to WC1 genes of cattle, and for variation among goat breeds. We found sequence for 17 complete WC1 genes and evidence for up to 30 SRCR a1 or d1 distinct signature domains suggesting potentially more WC1 genes. This is substantially more than in cattle. Goats had seven different WC1 gene structures of which 4 are unique to goats. Caprine WC1 genes also had multiple transcript splice variants of their intracytoplasmic domains that eliminated tyrosines shown previously to be important for signal transduction. The most distal WC1 SRCR domains known as SRCR a1, based on sequence and position, were highly conserved among goat breeds but fewer were conserved between goats and cattle. Conclusions. Goats have a greater number of WC1 genes and unique WC1 gene structures relative to cattle as well as splice variants of transcripts for intracytoplasmic domains that do not occur in cattle. Thus, goat WC1 molecules may have expanded functions. This finding may impact research on next generation vaccines designed to stimulate gd T cells.